CB-839 + Capecitabine in Solid Tumors and Fluoropyrimidine Resistant PIK3CA Mutant Colorectal Cancer

Inclusion Criteria

• Phase I
• Patients must have an advanced solid tumors for whom there are no remaining treatment options or colorectal patients who have progressed on front-line fluoropyrimidine containing therapy. Patients with colorectal cancer must have progressed on at least one line of fluoropyrimidine containing therapy. Receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting for all colorectal cancer patients unless either of these agents are otherwise contraindicated in the opinion of the treating physician. Prior regorafenib or TAS-102 therapy is not required.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dl
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Serum creatinine ≤ 1.5 X institutional upper limit of normal
• Total bilirubin ≤ 1.5mg/dL
• Aspartate Aminotransferase (AST) serum glutamic oxaloacetic transaminase (SGOT) ≤ 2.5 X institutional upper limit of normal
• Alanine Aminotransferase (ALT) serum glutamic pyruvic transaminase (SGPT) ≤ 2.5 x institutional upper limit of normal
• Patients must be able to swallow pills.
• Patients must have the ability to understand and the willingness to sign a written informed consent document.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>45 years old and without menses for >1 year) and surgically sterilized females are exempt from these requirements. Male patients must use an effective barrier method of contraception during the study and for a minimum of 3 months following the last dose of study drug if sexually active with a female of childbearing potential.
• Phase II
• Patients must have histologically or cytologically confirmed, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutant metastatic colorectal cancer. PIK3CA status must be confirmed by tumor sequencing in a CLIA certified lab.
• Patients must have measurable disease according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria that is amenable to biopsy and be willing to undergo pre- and post-treatment tumor biopsies. Lesions to be biopsied do not have to be those used for measurement.
• Patients must have received and progressed on fluoropyrimidine or fluoropyrimidine based therapy. Receipt of either oxaliplatin or irinotecan in combination with a fluoropyrimidine is required in the front line setting unless either of these agents are otherwise contraindicated in the opinion of the treating physician in which case a fluoropyrimidine only may be used. Prior regorafenib or TAS-102 therapy is not required.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Patients must have normal organ and marrow function as defined below:
• Hemoglobin ≥ 9.0 g/dl
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelet count ≥ 100,000/mcL
• Serum creatinine within normal institutional limits
• Total bilirubin ≤ 1.5 mg/dL
• AST (SGOT) ≤ 2.5 X institutional upper limit of normal
• ALT (SGPT) ≤ 2.5 x institutional upper limit of normal
• Patients must be able to swallow pills.
• Patients must have the ability to understand and the willingness to sign a written informed consent document.
• Female patients of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to the first dose of study drug and agree to use dual methods of contraception during the study and for a minimum of 3 months following the last dose of study drug. Post-menopausal females (>45 years old and w